Health Benefits of Turmeric/Curcumin · Health Benefits of Turmeric/Curcumin Shobha Ghosh, PhD,...

Department of Internal Medicine, VCU Medical Center, Richmond, VA 23298-0050

Health Benefits of Turmeric/Curcumin

Shobha Ghosh, PhD, FAHAProfessor of Medicine and Physiology

Department of Internal Medicine


Clinical Trials with CurcuminTarget

Disease# Dose of Curcumin Findings

Obesity 2 1 g/day for 4 weeks500 mg/day for 12 weeks

Reduced IL-1β, IL-4, VGEFReduced LDL and lipid peroxidation

Metabolic syndrome

2 2 g/day for 12 weeks45-180 mg/day

Reduced LDL, TGNo effect

Diabetes 3 Meriva® (200mg/day) for 4 weeks200 mg/day for 9 months to pre-diabetics500 mg/day for 15-30 days

Improved blood flow in skin and retinaPrevention of diabetes developmentReduction in oxidative status

Fatty liver disease

2 Meriva® (1 g/day) for 8 weeks

70 mg/day for 8 weeks

Reduced BMI, waist circumference, and improved liver functionReduced liver fat, improved liver function

Cancer 13 6g/day with docetaxel for 6 cycles2g/day with radiotherapy

Dose escalation up to 8 g/day with docetaxel

Theracurmin (200 mg – 8 g) with Gemcitabine

Reduced PSA in this resistant populationReduces radiation dermatitis (Breast cancer patients)Increased tolerance to docetaxel and reduced cancer (metastatic breast cancer)Plasma levels in ng/ml range, reduced inflammation and some protection but curcumin well tolerated at these high doses (Abdominal fullness, diarrhea)

Depression 6 2 g/day along with anti-depressives

500 mg/day Curcumin with Fluoxetine

Reduced cytokines but increased brain derived-neurotropic factor; improved depression scoresFaster recovery

Arthritis 5 Theracurmin (150 mg/day) for 8 weeksFexofytol® (42 mg/day) for 3 monthsMeriva® (200 mg/day) for 3-8 months

Curcumin (500 mg/day) with diclofenac

Reduced knee pain scoreReduced pain and plasma cartilage specific markerReduced arthritis score and plasma CRP; reduced use of painkillersHigher improvement in pain scores


One major problem

• Curcumin is very poorly absorbed – even after 8 g/day, only ng levels can be detected in the plasma

• Therefore, the causal role of curcumin or definitive mechanism of action has not been established by animal studies

• Most studies demonstrating beneficial effects of curcumin are performed using cells and these effects are observed with much higher concentrations of curcumin than can be detected in the plasma

• Efforts are, therefore, directed towards making more curcumin available to the target cells

We hypothesized that curcumin may be acting in the intestine and therefore, its absorption may not be

necessary


• Intestine contains millions of bacteria that produce toxins (LPS)

• Neither the bacteria nor the toxin is released into the circulation

• Intestinal wall regulates this process and provides a barrier• If this barrier was not present, the amount of bacterial

toxins in the gut are enough to kill a human being!!• If the intestinal barrier is breached and the intestinal

bacteria or the bacterial products are released into the circulation slowly, it will cause inflammation and result in the development of diseases such as diabetes or heart or kidney disease

Rationale for our hypothesis


LPS (Active)

Dephos. LPS(Inactive)


Curcumin protects the Intestinal Barrier

No additions +LPS+Curcumin+LPS

Actin

Claudin-1

ZO-1

Claudin-7

20 µm AJP (2017)


Clinical Trials with Curcumin

Chow WD+CWD

Work in progress


Clinical Trials with Curcumin

Work in progress

WDWD

Activity

Disrupts

MΦsInflammationPermeability

LPS

MΦ Activation MΦ infiltration into artery wall

MΦ infiltration into adipose

tissue

T2DM Atherosclerosis


Department of Internal Medicine, VCU Medical Center, Richmond, VA 23298-0050PLoS One. 2014 Sep 24;9(9):e108577

Proposed model for the action of Curcumin

Curcumin

Heart DiseaseDiabetesKidney disease


Thank you for your attention

Effect of Curcumin on Chronic Kidney Disease

Control: Sham surgery

NX: 5/6th

Nephrectomy

Supplementation with Curcumin or

Enalapril


•Collect Plasma•Collect urine•Evaluate Kidney Function


Supplementation with curcumin attenuates Kidney Disease

• Nx – Animal model for kidney disease

• Enalapril – Currently used drug for kidney disease

Ghosh SS et el: Am J Physiol Renal Physiol. 296:F1146-57, 2009

Effect of Curcumin on Diabetes and Heart Disease

Perform Glucose Tolerance test to evaluate diabetes

Fed a High Fat High Cholesterol (Western Diet) for 16 weeks with or

without oral curcumin

Mice SacrificedEvaluate Atherosclerosis


LDLR-/- Mice


Supplementation with curcumin attenuates Western Diet-induced Diabetes and heart

disease

Ghosh SS et al. PLoS One. 9(9):e108577, 2014


LP

S (E

U/m

l)

Chow WD0

1

2

3

4*

Spec

ific

Activ

ity(%

Cho

w C

ontro

l)

Chow WD0

50

100

*

FITC

(ng/µ l

)

Chow WD0.0

0.5

1.0

1.5

2.0

2.5 *

Western Diet feeding promotes translocation of bacterial toxin (LPS) to circulation


Supplementation with curcumin attenuates WD-induced increase in plasma LPS levels


Systemic Circulation

Lumen

Outer MucinInnerMucinCell

Layer

1

4

3

2

Dire

ctio

n of

mov

emen

t of b

acte

ria/b

acte

rial

prod

ucts

IAP

Anti-Bacterial Proteins

PanethCells

Goblet Cells

LPS (Active)

Dephos. LPS(Inactive)

Health Benefits of Turmeric/Curcumin · Health Benefits of Turmeric/Curcumin Shobha Ghosh, PhD,...

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